P518: VENETOCLAX AND AZACITIDINE COMBINED WITH CHIDAMIDE (VAC) FOR THE TREATMENT OF NEWLY DIAGNOSED ACUTE MONOCYTIC LEUKEMIA PATIENTS
Authors: Zheng LI, Hao Zhang, Yanyan LI, Lulu Chen, Haiping Dai, Haixia Zhou, Mingzhu Xu, Tongtong Zhang, Chongsheng Qian, Wenjie Gong, Qiaocheng Qiu, Aining Sun, Depei Wu, Shengli Xue
Journal: HemaSphere (2023)

Background: The emergence of resistance to Venetoclax-based combinations for whom intensive chemotherapy is not suitable has become an important clinical dilemma. Some studies have found that the overall remission rate (ORR) of acute monocytic leukemia (AML-M5) patients receiving Venetoclax plus Azacitidine (VA) was only 40%. Myeloid cell leukemia 1 (MCL1) plays a critical role in the regulation of cell apoptosis, and high expression of MCL1 has been observed in acute AML-M5. Chidamide, a new selective histone deacetylase inhibitor, has been shown to decrease the protein level of MCL1 and overcome drug resistance to a certain extent. Aims: This study was to investigate the therapeutic safety and efficacy of VAC for newly diagnosed (ND) AML-M5 patients who are ineligible for or decline to undergo intensive chemotherapy. Methods: ND AML-M5 patients who were ineligible for or chose not to undergo intensive chemotherapy were enrolled.For the first cycle of treatment, patients were administered 10 mg of Chidamide orally daily for 7 days, 75 mg/m2 of Azacitidine subcutaneously daily for 7 days, and Venetoclax orally daily (100 mg on d1, 200 mg on d2, 400 mg on d3–d28). Disease state was assessed on d21-d28 through bone marrow aspiration. The second cycle of treatment, which was either VAC or other chemotherapy, was started at that time regardless of disease state. For post-remission therapy, patients could continue to receive VAC or other regimens, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be performed on eligible patients. Results: Between March 10, 2022, and August 12, 2022, 13 ND AML-M5 patients (seven male and six female) were enrolled. The median age was 53 years (range, 16–63) (Table 1). During cycle 1, 12 (92.3%) of these 13 patients achieved CRc (CR+CRi+MLFS), and one patient (7.7%) with TP53 mutation reached NR. Ten (81.8%) of the 12 patients who achieved CRc had measurable residual disease (MRD) negativity as assessed by multiparameter flow cytometry with a sensitivity of 10-4. As of the cut-off date, January 31, 2023, five patients who achieved CRc underwent the second cycle of the VAC regimen. The CRc rates in patients with favorable, intermediate, and adverse risk as categorized by the 2022 ELN were 100% (5/5), 100% (3/3), and 80% (4/5), respectively. At a median follow-up of 7.0 months (range, 1.4–10.6), the median OS and EFS were not reached. The estimated 12-month OS was 67.7% (95% CI, 51–84) and EFS was 69.2% (95% CI, 57–81) (Figure 1). One patient died of disease progression, and one patient experienced relapse after one cycle of VAC and consolidation without allo-HSCT. Three (23.1%) of 13 patients received haploidentical HSCT at CR1. One patient died of severe infection after allo-HSCT, and the other two patients are still alive. Notable serious adverse events were pneumonia, observed in two (15.4%) patients, and sepsis, observed in one (7.7%) patient. The treatment-related mortality (TRM) rates were 7.7% (1/13) as of 8 weeks. In cycle 1, 12 patients received blood transfusions. Conclusion: The VAC regimen was an effective low-intensity regimen that was well tolerated by this cohort of ND AML-M5 patients who were either ineligible for or declined to undergo intensive chemotherapy. Even one cycle could produce high rates of CR and encouraging OS and EFS results.Keywords: Acute monoblastic leukemia, Acute myeloid leukemia